Immunoglobulin (Ig) allotypes are inherited in Mendelian fashion. Such behavior is generally interpreted to mean that allelic structural genes encode for each alternative form of a given Ig class or subclass. However, deviations from expected allelic behavior, i.e., the transient appearance of allotypes normally undetectable (hidden allotypes), have been reported by us and others. These observations have raised basic questions as to the genetic control of Ig allotypes. For example, does a regulatory control mechanism permit only one of several possible allotypes to be expressed? Are allotypes the products of non-allelic structural genes, the control of which mimics a Mendelian pattern of segregation? Are the regulatory control genes leaky? By means of our recently adapted radioimmune assay, we can detect in the serum of normal Ig-congenic mice an allotype antigen that these mice were bred to exclude. Consistent with our early findings, this "wrong" allotype is not always detectable but can represent as much as 0.3% of the total 7S Ig fraction. To characterize this hidden allotype further, we will measure its rate of association to anti-allotype antibody and is rate of dissociation vs. a reference allotype. Also, we will continue our efforts to "turn-on" experimentally the production of hidden allotypes in Ig-congenic mice. Success in this endeavor would provide insight into the regulatory control mechanisms for Ig production.